Recellularization of Liver Bioscaffolds

肝脏生物支架的再细胞化

• 批准号: 9754808
• 负责人: Basak Elif Uygun
• 金额: $ 39.54万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-05 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9754808
• 关键词: Address; Affinity; Architecture; Biliary; Binding; Biomaterials Research; Blood Vessels; Cells; Cessation of life; Collagen; Cues; Data; Development; Elastin; Endothelial Cells; Endothelium; Engineering; Epithelial Cells; Extracellular Matrix; Extrahepatic Bile Ducts; Future; Goals; Graft Survival; Health; Hepatic; Hepatic Mass; Hepatocyte; Human; Image Analysis; In Vitro; Kidney; Lead; Liver; Liver Dysfunction; Liver Failure; Liver Regeneration; Liver diseases; Location; Modeling; Organ; Organ Donor; Organ Model; Organ Transplantation; Pancreas; Peptides; Perfusion; Protocols documentation; Public Health; Rattus; Research; Seeds; System; Techniques; Testing; Time; Tissue Engineering; Transplantation; Vascular Endothelial Cell; Waiting Lists; Work; base; bile duct; biliary tract; blood perfusion; cell type; clinical translation; density; end-stage organ failure; graft function; in vivo; liver function; liver transplantation; neglect; next generation; novel strategies; public health relevance; scaffold; success; thrombogenesis

Abstract About thirty million people in the US have some type of liver disorder, and about 27,000 deaths are registered annually due to liver disease. At this time, the only definitive treatment of hepatic failure is orthotopic transplantation. However, there is a critical shortage of organs with a continual deficit of >4,000 livers per year. Given that only organs in pristine condition are transplantable, orthotopic transplantation will always remain a limited pool. Recent advances in tissue engineering through the use of decellularized liver scaffolds have opened the possibility that engineered liver grafts could be used as substitutes for donor livers, potentially addressing the shortage of organs available for transplantation. However, the road to clinical translation is expected to be long due to the wide range of functions the engineered liver is required to capture, for example, those represented by the biliary system have been neglected thus far. Furthermore, long term transplantation of engineered liver grafts has not been successful due to thrombogenicity of the recellularized grafts. We plan to engineer transplantable liver grafts for treating liver dysfunction and failure through the completion of the following specific aims 1) Enhance endothelialization efficiency of rat liver grafts, 2) Repopulate bile ducts of rat livers and 3) Develop a liver graft that functions in vivo. The work described here is expected to result in the next generation engineered liver grafts incorporating parenchymal and non-parenchymal components to provide auxiliary hepatic support.

摘要 在美国大约有三千万人患有某种类型的肝脏疾病，大约有27,000人死亡 每年因肝病。目前，肝衰竭唯一确定的治疗方法是原位肝移植 移植然而，器官严重短缺，每年持续短缺超过4，000个肝脏。 鉴于只有原始状态下的器官才可移植，原位移植将始终是一种治疗方法。 泳池有限。通过使用脱细胞肝脏支架的组织工程的最新进展已经 开辟了工程肝脏移植物可用作供体肝脏替代品的可能性， 解决可用于移植的器官短缺问题。然而，临床翻译之路是 由于工程化肝脏需要捕获的广泛功能，例如， 以胆道系统为代表的疾病迄今为止一直被忽视。长期移植 由于再细胞化移植物的血栓形成性，工程化肝移植物的应用尚未成功。我们计划 设计可移植肝脏移植物，通过完成 具体目标如下：1）增强大鼠肝移植物的内皮化效率，2）重建大鼠胆管 肝脏和3）开发在体内发挥功能的肝脏移植物。这里所描述的工作预计将导致 下一代工程化肝移植物结合实质和非实质成分， 提供辅助肝脏支持。